ABSTRACTThe analysis of plasma kinetics of the sympathetic neurotransmitter norepinephrine can be used to estimate sympathetic nervous “activity” (integrated nerve firing rate) for the body as a whole and for individual organs. In 12 patients with cardiac failure (left ventricular ejection fraction 10 % to 39 %), the mean arterial plasma norepinephrine concentration was 557 + 68 pg/ml (mean SE) compared with 211 + 21 pg/ml in 15 subjects without heart failure (p < .002). The difference was due to both increased release of norepinephrine to plasma (indicating increased “total” sympathetic activity) and reduced clearance of norepinephrine from plasma. The increase in sympathetic activity did not involve all organs equally. Cardiac (32 ± 9 vs 5 ± 1 ng/min; p <.002) and renal (202 ± 45 vs 66 ± 9 ng/min; p = .002) norepinephrine spillover were increased by 540% and 206%, respectively, but norepinephrine spillover from the lungs was normal. Adrenomedullary activity was also increased in the patients with heart failure, whose mean arterial plasma epinephrine concentration was 181 + 38 pg/ml compared with 71 ± 12 pg/ml in control subjects (p < .02). There is marked regional variation, inapparent from measurements of plasma norepinephrine concentration, in sympathetic nerve activity in patients with congestive heart failure. The finding of increased cardiorenal norepinephrine spillover has important pathophysiologic and therapeutic implications.